SLC4A1 Chromosome 17
Solute carrier family 4 member 1 (Diego blood group)
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What This Gene Does
The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis. [provided by RefSeq, Jul 2008]
Gene Info
Gene Group
"Blood group antigens|CD molecules|Solute carrier family 4"
Locus Type
gene with protein product
Location
17q21.31
Ensembl
ENSG00000004939
Associated Conditions (24)
Hereditary spherocytosis type 4
11 conditions
Autosomal dominant distal renal tubular acidosis
SWANN BLOOD GROUP ANTIGEN
Hemolytic anemia
Acanthocytosis due to band 3 HT
Acanthocytosis
SLC4A1-related disorder
Renal tubular acidosis
distal
4
with hemolytic anemia
Inborn genetic diseases
Cryohydrocytosis
Distal renal tubular acidosis
Autosomal recessive distal renal tubular acidosis
BLOOD GROUP--WRIGHT ANTIGEN
with normal red cell morphology
BLOOD GROUP--DIEGO SYSTEM
Southeast Asian ovalocytosis
+4 more conditions
Key Variants
RS121912741
Conflicting classifications of pathogenicity
Hereditary spherocytosis type 4, Hereditary spherocytosis type 4, 11 conditions
Health Risk
RS121912749
Conflicting classifications of pathogenicity
Hereditary spherocytosis type 4, Autosomal dominant distal renal tubular acidosis, 11 conditions
Health Risk
RS121912757
Conflicting classifications of pathogenicity
SWANN BLOOD GROUP ANTIGEN, Autosomal dominant distal renal tubular acidosis, Hemolytic anemia
Health Risk
RS121912759
Conflicting classifications of pathogenicity
Acanthocytosis due to band 3 HT, Acanthocytosis, Hemolytic anemia
Health Risk
RS13306774
Conflicting classifications of pathogenicity
Hereditary spherocytosis type 4, Hereditary spherocytosis type 4
Health Risk
RS13306776
Conflicting classifications of pathogenicity
Hereditary spherocytosis type 4, Autosomal dominant distal renal tubular acidosis, Hemolytic anemia
Health Risk
RS1362663440
Conflicting classifications of pathogenicity
Hereditary spherocytosis type 4, Hereditary spherocytosis type 4
Health Risk
RS138242019
Conflicting classifications of pathogenicity
Autosomal dominant distal renal tubular acidosis, Hereditary spherocytosis type 4, Hemolytic anemia
Health Risk
RS139308660
Conflicting classifications of pathogenicity
Autosomal dominant distal renal tubular acidosis, Hereditary spherocytosis type 4, Hemolytic anemia
Health Risk
RS141605301
Conflicting classifications of pathogenicity
Autosomal dominant distal renal tubular acidosis, Hemolytic anemia, Hereditary spherocytosis type 4
Health Risk
RS142161945
Conflicting classifications of pathogenicity
Health Risk
RS142757938
Conflicting classifications of pathogenicity
Health Risk
All Variants (205)
| RSID | Category | Clinical Significance | Conditions |
|---|---|---|---|
| RS2509962547 | Health Risk | Likely pathogenic | — |
| RS2509962733 | Health Risk | Likely pathogenic | — |
| RS2509962789 | Health Risk | Likely pathogenic | — |
| RS2509964040 | Health Risk | Likely pathogenic | — |
| RS2509964271 | Health Risk | Likely pathogenic | — |
| RS2509965507 | Health Risk | Likely pathogenic | SLC4A1-related disorder, SLC4A1-related disorder |
| RS2509966235 | Health Risk | Likely pathogenic | — |
| RS2509966572 | Health Risk | Likely pathogenic | SLC4A1-related disorder, SLC4A1-related disorder |
| RS2509966742 | Health Risk | Likely pathogenic | — |
| RS2509967246 | Health Risk | Likely pathogenic | — |
| RS2509967374 | Health Risk | Likely pathogenic | — |
| RS2509967379 | Health Risk | Likely pathogenic | — |
| RS2509967589 | Health Risk | Likely pathogenic | — |
| RS2509968215 | Health Risk | Likely pathogenic | — |
| RS2509968418 | Health Risk | Likely pathogenic | — |
| RS2509968499 | Health Risk | Likely pathogenic | SLC4A1-related disorder, SLC4A1-related disorder |
| RS2509968564 | Health Risk | Likely pathogenic | — |
| RS2509969653 | Health Risk | Likely pathogenic | — |
| RS2509970932 | Health Risk | Likely pathogenic | — |
| RS2509970954 | Health Risk | Likely pathogenic | — |
| RS2509971147 | Health Risk | Likely pathogenic | — |
| RS372033718 | Health Risk | Likely pathogenic | — |
| RS45519733 | Health Risk | Likely pathogenic | Autosomal dominant distal renal tubular acidosis, Autosomal dominant distal renal tubular acidosis |
| RS575655181 | Health Risk | Likely pathogenic | Autosomal dominant distal renal tubular acidosis, Autosomal dominant distal renal tubular acidosis |
| RS756316460 | Health Risk | Likely pathogenic | — |
| RS778311783 | Health Risk | Likely pathogenic | — |
| RS1057518222 | Health Risk | Pathogenic | — |
| RS1162787335 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS121912742 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS121912744 | Health Risk | Pathogenic | Autosomal dominant distal renal tubular acidosis, Distal renal tubular acidosis, Inborn genetic diseases |
| RS121912746 | Health Risk | Pathogenic | Autosomal dominant distal renal tubular acidosis, Autosomal dominant distal renal tubular acidosis |
| RS121912752 | Health Risk | Pathogenic | Renal tubular acidosis, distal, 4 |
| RS121912753 | Health Risk | Pathogenic | Renal tubular acidosis, distal, with normal red cell morphology |
| RS121912754 | Health Risk | Pathogenic | Renal tubular acidosis, distal, 4 |
| RS1472653057 | Health Risk | Pathogenic | — |
| RS1555596072 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS1555596483 | Health Risk | Pathogenic | — |
| RS1555596757 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS1598299485 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS1598302037 | Health Risk | Pathogenic | — |
| RS2047371081 | Health Risk | Pathogenic | — |
| RS2047398183 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS2047401561 | Health Risk | Pathogenic | — |
| RS2047420220 | Health Risk | Pathogenic | — |
| RS2144594807 | Health Risk | Pathogenic | Autosomal dominant distal renal tubular acidosis, Autosomal dominant distal renal tubular acidosis |
| RS2144596569 | Health Risk | Pathogenic | — |
| RS2144601154 | Health Risk | Pathogenic | Hereditary spherocytosis type 4, Hereditary spherocytosis type 4 |
| RS2144615066 | Health Risk | Pathogenic | — |
| RS2144625139 | Health Risk | Pathogenic | — |
| RS2509957512 | Health Risk | Pathogenic | — |